bcg in combination with durvalumab in adult bcg-naïve, high-risk nmibc participants

Conditions: Non-Muscle- Invasive Bladder Cancer

Summary: the purpose of this study is to assess the safety, tolerability, and efficacy profile of durvalumab + bcg (induction and maintenance) combination therapy in adult united states participants with a histologically confirmed diagnosis of high-risk non-muscle-invasive bladder cancer (nmibc), who have received no prior systemic therapy for nmibc, and who are bcg-naïve.

this is an open-label, single-arm, multi-center, phase iiib us study exploring the combination of durvalumab and bcg (induction and maintenance) in participants with high-risk nmibc. each participant will have screening activities up to 4 weeks before initiation of study intervention, receive study intervention for up to 24 months, followed by 3 months safety follow-up. participants will continue to be followed up for survival until 2 years from the date of treatment initiation of the last participant enrolled in this study (approximately 42 months after first participant enrolled).

Eligibility criteria:
inclusion criteria: * bcg-naïve (defined as participants not having received prior intravesical bcg or who previously received but stopped bcg more than 3 years before study entry). * local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. * complete resection of all ta/t1 papillary disease prior to enrollment, with the transurethral resection of bladder tumor (turbt) removing high-risk nmibc (non-muscle invasive bladder cancer) performed not more than 4 months before enrollment in the study. * no prior radiotherapy for bladder cancer. * a life expectancy of at least 12 weeks (90 days). * adequate organ and marrow function * world health organization/eastern cooperative oncology group performance status of 0 or 1 at screening * no prior exposure to immune-mediated therapy of cancer * a candidate for bcg treatment. * local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. a high-risk tumor is defined as one of the following: t1 tumor; high-grade/g3 tumor; cis. exclusion criteria: * evidence of muscle-invasive, locally advanced, metastatic, and/or extra-vesical bladder cancer (ie, t2, t3, t4, and / or stage iv). * predominantly variant histology such as micropapillary, plasmacytoid, nested, sarcomatoid, microcystic, squamous and adeno variants of uc representing \> 50% of tumor tissue or other than urothelial tumors as assessed by pathology. * evidence of lymphovascular invasion of bladder tumor, except if treatment with bcg is deemed to be the only clinically viable treatment. * immediate cystectomy is indicated. * known or documented absolute and/or relative contraindication of adjuvant intravesical bcg treatment. * concurrent extravesical, non-muscle-invasive transitional cell carcinoma of the urothelium. * history of allogenic organ transplantation. participants with any history of allogenic stem cell transplantation are also excluded. * active or prior documented autoimmune or inflammatory disorders. * participants with hypothyroidism stable on hormone replacement. * history of active primary immunodeficiency. * active infection including hepatitis b (known positive hbv/hbsag result), hcv, or hiv 1/2 (positive hiv) antibodies. * current or prior use of immunosuppressive medication within 14 days before the first durvalumab dose. * female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ highly effective birth control. * any concurrent chemotherapy, study intervention, biologic or hormonal therapy for cancer treatment; uncontrolled intercurrent illness; * history of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥ 2 years; adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cis without evidence of disease; prostate cancer of stage ≤ t2cn0m0 without biochemical recurrence or progression that in the opinion of the investigator does not require active intervention. * previous or concurrent treatment with potent systemic immunostimulatory agents

Keywords: bacillus calmette-guerin (bcg) bcg-naïve immunotherapeutics human mab durvalumab non-muscle-invasive bladder cancer (nmibc)